Interferons are glycoproteins produced by a wide range of vertebrate cells in response to viral infection. They are also induced by various non-viral stimuli, such as polyriboinosinic:polyribocytidylic acid (poly 1:poly C) and specific antigens upon exposure to sensitized lymphocytes. Although interferons were initially thought to be specific inhibitors of viral replication, accumulating evidence suggests that they also have potent effects on cellular function. These include alterations in cellular proliferation, immunologic responses, and enzymatic activity. Tumor growth is inhibited and survival is prolonged in both transplantable and carcinogen-induced tumor models. Trails with interferon as an antitumor compound in man have been initiated in osteosarcoma, breast carcinoma, lymphonas, myelomas, and melanomas. Preliminary results of these have been encouraging. Our laboratory has developed and studied many of the animal bladder carcinoma models currently utilized for experimental investigation. These carcinomas are induced by the carcinogens, N-(4-(5-nitro-2-furyl)-2-thiazolyl)formamide(FANFT), N-butyl-N-(4-hydroxbutyl)nitrosamine(BBN), and bracken fern (BF). They are transplantable either subcutaneously or intravesically. Although only a limited number of investigations have been performed, therapeutic studies utilizing these models have found that drugs active in murine bladder carcinoma are active in man. It is our intent to determine the activity of interferons and the potent interferon inducer, poly l:poly C, in these models. Effects on both carcinogen-induced and transplantable bladder carcinomas will be determined. Tumors will be implanted subcutaneously and intravesically. Both local and systemic routes of treatment will be evaluated. Our results should provide critical data for future use in Phase II decisions concerning trails with interferon and its inducers in human bladder carcinoma.